The toxicopathologic and pharmacologic effects of symmetrical hexachlorobiphenyls (HCBs) were studied in chickens and mice. The HCBs represent model PCBs with high and constant chlorine content permitting unequivocal study of a given substitution pattern. Separate and distinct differences in isomer toxicity were observed, and one could differentiate a chlorinated dibenzofuran effect from any HCB studied (in chicks). Although certain toxicologic and pharmacologic characteristics differentiate the biological responses in each species tested, the major effects were common to both chicks and mice. These isomer differences in biological response can be related to chemical structure.